Purine auxotrophy is an abundant trait among eukaryotic parasites and a typical marker for many budding yeast strains. Supplementation with an additional purine source (such as adenine) is necessary to cultivate these strains. If not supplied in adequate amounts, purine starvation sets in. We explored purine starvation effects in a model organism, a budding yeast Saccharomyces cerevisiae ade8 knockout, at the level of cellular morphology, central carbon metabolism, and global transcriptome. We observed that purine-starved cells stopped their cycle in G1/G0 state and accumulated trehalose, and the intracellular concentration of AXP decreased, but adenylate charge remained stable. Cells became tolerant to severe environmental stresses. Intracellular RNA concentration decreased, and massive downregulation of ribosomal biosynthesis genes occurred. We proved that the expression of new proteins during purine starvation is critical for cells to attain stress tolerance phenotype Msn2/4p targets are upregulated in purine-starved cells when compared to cells cultivated in purine-rich media. The overall transcriptomic response to purine starvation resembles that of stationary phase cells. Our results demonstrate that the induction of a strong stress resistance phenotype in budding yeast can be caused not only by natural starvation, but also starvation for metabolic intermediates, such as purines.

Purine starvation induces a quiescence-like and stress-resistant physiological state in Saccharomyces cerevisiae , but it remains unclear whether this response is uniform across all disruptions of the de novo adenine biosynthetic pathway. Here, we used a pathway-position series of adenine-biosynthesis deletion mutants to test how the location of the metabolic blockage shapes cellular adaptation to purine starvation, using nitrogen starvation as a reference condition. Across mutants, purine starvation induced a shared core response marked by reduced growth, repression of ribosome-biogenesis and rRNA-processing modules, and accumulation of cells in G1/G0 phase. However, the magnitude and composition of the response varied systematically with pathway position. Early-pathway mutants showed the strongest desiccation tolerance and stress-associated transcriptional remodelling, whereas late-pathway mutants showed weaker protection. The ade16Δade17Δ double mutant was a distinct outlier, with altered carbon-flux distribution and limited stress resilience, suggesting that late-pathway disruption produces a physiologically different starvation state. Transcriptome analysis showed partial overlap with nitrogen starvation, but also pathway-position-dependent regulation of metabolic, ribosome-related, mitochondrial, and stress-response modules. Together, these results indicate that purine starvation is not a single physiological condition, but a set of related starvation states shaped by the position of the metabolic block within the purine biosynthetic pathway.